Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are several neuropeptides, present in nerves supplying the rat adrenal zona glomerulosa, which have been shown to stimulate aldosterone secretion in the intact perfused rat adrenal preparation. The purpose of the present study was twofold: first, to determine whether these peptides acted directly on adrenocortical cells by examining their effects on collagenase-dispersed rat zona glomerulosa cells, and second, to investigate the likely physiological significance of these actions, by determining whether the responses of zona glomerulosa cells to neuropeptides were changed by prior sodium depletion. Of the peptides tested, neuropeptide Y (NPY) and substance P had only a minor effect on aldosterone secretion, which was not substantially affected by sodium depletion. Corticotrophin-releasing hormone (CRH) had a significant stimulatory effect on aldosterone secretion, but neither the threshold concentration for significant stimulation nor the maximal response to stimulation were altered by prior sodium depletion. Vasoactive intestinal peptide (VIP), on the other hand, had little effect on aldosterone secretion by cells from normal animals, but was a potent stimulus to aldosterone secretion in cells obtained from sodium-depleted animals. The response to the Met-enkephalin analogue, [D-Ala2-Met2]-enkephalinamide (DALA), was also significantly enhanced by prior sodium depletion. Experiments using the angiotensin II receptor blocker, saralasin, were carried out to determine whether the enhanced actions of DALA and VIP seen in sodium depletion may be a result of activation of angiotensin II receptors, known to be increased in sodium depletion. Saralasin did not affect the response to either peptide. These data suggest that all the peptides tested may be able to stimulate aldosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of sodium depletion on the response of rat adrenal zona glomerulosa cells to stimulation by neuropeptides: actions of vasoactive intestinal peptide, enkephalin, substance P, neuropeptide Y and corticotrophin-releasing hormone. 756 31

Peptidergic nerves in immune organs and lymphoid tissues of the lungs and gastrointestinal tract end on or in close proximity to lymphocytes, mast cells and macrophages. Vasoactive intestinal peptide, substance P and some other neuropeptides, that are recognized by distinct sets of cell surface receptors, regulate aspects of T cell differentiation in the thymus, such as negative selection, and contribute to mediating compartmental immune responses. The latter effects include stimulating expression of adhesive proteins by lymphocytes, enhancement of lymphocyte and macrophage migration in vascular and connective tissues, and modulation of proliferative and synthetic responses of lymphocytes to diverse antigens.
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PMID:Neuropeptide signaling of lymphocytes in immunological responses. 761 31

1. We investigated the effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the peptidase alpha-chymotrypsin on non-adrenergic, non-cholinergic (NANC neural) bronchoconstriction induced by electrical stimulation of the vagus nerves and by capsaicin in anaesthetized guinea-pigs in vivo using pulmonary insufflation pressure (PIP) as an index of bronchial tone. We also investigated the contribution of soluble guanylyl cyclase (SGC) to NANC neural relaxant mechanisms. 2. In the presence of atropine and propranolol, electrical stimulation of the vagus nerves induced a frequency-dependent increase in PIP above baseline of 67% at 2.5 Hz, of 128% at 5 Hz and of 230% at 10 Hz. L-NAME (1-50 mg kg-1, i.v.), at doses inducing increases in systemic blood pressure, dose-relatedly potentiated NANC bronchoconstriction. At 10 mg kg-1 i.v., L-NAME significantly (P < 0.05) potentiated NANC bronchoconstriction by a further 106% at 2.5 Hz and a further 147% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. L-NAME did not induce bronchoconstriction in sham-stimulated control animals. D-NAME did not potentiate NANC bronchoconstriction. Raising systemic blood pressure with phenylephrine did not potentiate vagally-induced bronchoconstriction (2.5 Hz). 3. The NO precursor L-arginine, but not D-arginine, (100 mg kg-1, i.v.) significantly reversed the potentiation by L-NAME of NANC bronchoconstriction. L-Arginine alone significantly inhibited neurogenic bronchoconstriction at 10 Hz (by 74%); the inhibition of 25% at 2.5 Hz was not significant. 4. L-NAME did not significantly affect the increases in PIP induced by intravenous substance P. neurokinin A (NKA) or capsaicin. 5. The inhibitor of SGC, methylene blue (10 mg kg', i.v.) potentiated (by 110-140%) NANC neural bronchoconstriction induced by lower frequencies of nerve stimulation and reversed the reduction in PIP induced by the SGC activator, sodium nitroprusside (SNP, 1.05 mg kg- 1, i.v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.
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PMID:Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase. 767 32

Quantitative determination of neuropeptides in biologic tissues by radioimmunoassay requires both an efficient extraction of neuropeptides as well as maintenance of immunochemical reactivity. Vasoactive intestinal peptide, substance P, and met5-enkephalin were chosen for this study because they are neuropeptides which appear to be involved in multiple physiologic systems. Since all three neuropeptides have a methionine residue within their amino acid sequence, oxidation of methionine to methionine-sulfoxide during the extraction process could diminish their immunochemical reactivity. Multiple factors that might be important in extracting these neuropeptides from canine intestine, including pH of the solvent, tissue homogenization, heating, and addition of enzyme inhibitors, were examined. Concentrations of vasoactive intestinal peptide-like immunoreactivity and substance P-like immunoreactivity were significantly higher in acidic solvents, and tissue homogenization appeared to increase the concentrations of these two neuropeptides. Substance P-like immunoreactivity was increased by heating after tissue homogenization, suggesting heat-induced denaturation of tissue enzymes liberated by homogenization. Separation of acidic tissue extracts by high performance liquid chromatography followed by radioimmunoassay for all three neuropeptides revealed minor acid-induced oxidation of substance P. These results should be useful for planning the extraction of these three neuropeptides from other tissues.
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PMID:Characterization of neuropeptides extracted from canine intestine. 768 77

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.
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PMID:Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors. 790 85

Accurate and sensitive sandwich ELISA has been developed for the detection and identification of each of the three neuropeptides, namely, Vasoactive intestinal peptide, Somatostatin and Substance P. The neuropeptides conjugated with BSA and emulsified with Freund's adjuvant were used for immunisation of rabbits. Titres of polyclonal antibodies were checked by indirect immunofluorescence. The animals were bled when titres were high, sera separated, complement inactivated and IgG class of antibodies were purified using a protein G column. Purified IgG antibodies were used for coating the wells and for conjugation with HRPO and used for the detection of the synthetic neuropeptides in a standard solution or in the culture supernatant. The ELISA thus developed for the assay of each of the three neuropeptides had a sensitivity (0.01 ng - 12.8 ng/ml) equal to or better than that reported for these peptides by radioimmunoassay. The assay was highly specific and did not react with a panel of other neuropeptides tested. High level of sensitivity without compromising the specificity was achieved by using activated polyvinyl plates and using purified IgG from high titre rabbit anti-peptide sera. The non specific reaction was minimised by using 10,000 MW cut off amicon filtered supernatants.
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PMID:New, sensitive and specific ELISA for the detection of neuropeptides in culture supernatants. 804 Mar 48

Ductal elements within salivary glands are responsible for modifying the electrolyte composition of primary saliva secreted by the acini. To study the mechanism and regulation of the transport processes involved requires a suitable preparation of functional ducts. To this end we have isolated intralobular ducts from rabbit mandibular salivary glands using the technique of tissue dissociation and microdissection. Light and electron microscopy demonstrated that the ducts corresponded ultrastructurally to striated intralobular ducts of the intact gland. Ducts could be maintained in tissue culture on polycarbonate filter rafts for up to 36 h, during which time the ends of the ducts did not usually seal. The overall resting content of ductal adenosine 3',5'-cyclic monophosphate (cyclic AMP) was 16.0 +/- 3.0 fmol mm-1 and increased dose dependently in response to stimulation with the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M; concentration required to produce a half-maximal response, K0.5 = 2.1 x 10(-6) M). The response to isoprenaline was blocked by the antagonist propranolol. Intracellular cyclic AMP content was also raised by the adenylate cyclase activator forskolin and by prostaglandin E2. Acetylcholine (3 x 10(-8)-10(-5) M) caused a dose-dependent and maintained rise in [Ca2+]i (K0.5 = 2.5 x 10(-7) M). This increase in [Ca2+]i could be reversed by the muscarinic antagonist atropine and appeared to result from a combination of mobilization of intracellular Ca2+ stores and entry of Ca2+ from the extracellular fluid. Noradrenaline induced only a very small, mainly transient rise in [Ca2+]i while phenylephrine failed to increase [Ca2+]i at all. Vasoactive intestinal peptide (5 x 10(-7) M) also produced a marginal, maintained rise in [Ca2+]i. Substance P, bombesin, isoprenaline, and prostaglandin E2 did not elevate [Ca2+]i. Application of the calcium ionophore ionomycin induced a substantial maintained rise in [Ca2+]i. Taken together, these results indicate that isolated and cultured striated ducts (i) possess intact beta-adrenoceptors coupled to adenylate cyclase, putative receptors for prostaglandin E2 and muscarinic receptors, and (ii) represent a viable preparation for the study of the transport mechanisms involved in the ductal modification of salivary fluid composition.
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PMID:Structural and functional characterization of striated ducts isolated from the rabbit mandibular salivary gland. 838 3

The regulation of pancreatic exocrine secretion involves hormonal, neural and neurohormonal components. Many agonists are known to be effective in pancreatic acinar cells, but less is known about the ducts. Therefore, we wanted to investigate the influence of various agonists on isolated perfused pancreatic ducts and, as a physiological response, we measured the basolateral membrane voltage of the duct cells (Vbl) with microelectrodes. Pancreatic ducts were dissected from pancreas of normal rats and bathed in a HCO(3-)(-containing solution. Under control conditions, the average Vbl was between -50 and -70 mV. Vasoactive intestinal peptide (VIP) and carbachol (CCH) reversibly depolarized Vbl when applied to the bath. VIP (9 x 10(-9) mol/l) depolarized Vbl from -72 +/- 3 mV to -53 +/- 3 mV (n = 20) and CCH (10(-5) mol/l) from -62 +/- 3 to -35 +/- 4 mV (n = 10). Furthermore, a decrease of the Cl- concentration in the lumen led to an increase of VIP-induced depolarization of Vbl, suggesting that a luminal Cl- conductance was increased. Cholecystokinin (CCK, 10(-10)-10(-7) mol/l) and bombesin (10(-8), 10(-5) mol/l), which stimulate pancreatic exocrine secretion in acini or whole glands, showed no significant effect on Vbl of the duct cells tested in our preparation (n = 7, 6). Neurotensin (10(-8) mol/l) had a marked depolarizing effect in two out of ten cases; Vbl depolarized from about -65 mV to -29 mV and the effect was reversible. Substance P (2 x 10(-7) mol/l), alone or in combination with secretin, had no effect on Vbl of the tested duct cells (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of vasoactive intestinal peptide, carbachol and other agonists on the membrane voltage of pancreatic duct cells. 841 20

In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL-2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo.
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PMID:Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements. 851 59

Mast cells are thought to be involved in neurogenic inflammation in skin, and numerous neuropeptides are known to degranulate mast cells. We monitored histamine release in skin in situ with the microdialysis method after skin challenge with neuropeptide injections (10 microM substance P, vasoactive intestinal peptide and calcitonin gene-related peptide), capsaicin injection (30 microM) and 0.1% capsaicin cream with a moist compress. Fractions were collected for 15 min each at 3.0 microliter/min. One hour after insertion of the probe, the baseline histamine level was 4.5 +/- 4.5 nM (mean +/- SD, n = 20). Substance P (250 pmol) induced histamine release peak (66.1 +/- 52.5 nM, n = 8) in the 0-15 or 15-30 min fraction. Thereafter, the histamine concentration declined steadily and rapidly and no second rise was observed. A single substance P injection was sufficient to induce major histamine release in three out of four experiments; and the release kinetics of the second injection (1 h later) mimicked that of the first injection. Vasoactive intestinal peptide (100 and 250 pmol) induced a rapid release of histamine in 4 subjects comparable to substance P, whereas calcitonin gene-related peptide (250 pmol) did not release detectable amounts of histamine in 2 subjects tested. Capsaicin induced a low and rather non-significant release of histamine in 4 out of 5 patients who received capsaicin injection and in 2 out of 5 who were treated with capsaicin cream. The present study shows that neuropeptides substance P and vasoactive intestinal peptide, but not calcitonin gene-related peptide, can induce activation of mast cells and release of histamine into the extracellular space. The low release of histamine by capsaicin suggests low levels of neuropeptides or infrequent morphological contacts between mast cells and sensory nerves in normal human skin. The microdialysis method can be used for studying skin inflammatory reactions involving mast cells.
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PMID:Neuropeptide- and capsaicin-induced histamine release in skin monitored with the microdialysis technique. 880 Mar


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